PROJECT SUMMARY/ABSTRACT Colorectal cancer is the second-leading cause of cancer death in the U.S. While research has shown that colorectal cancer screening decreases colorectal cancer incidence and mortality, only 65% of eligible adults were screened at the recommended interval in 2015. Even more troubling, those who are screened do not always get timely follow-up care for abnormal results. Dr. Lynn Butterly demonstrated that patient navigation can effectively raise rates of colonoscopy uptake among low-income, uninsured patients in New Hampshire, boosting rates 27 percentage points over usual care (96.2% vs 69.3%, P<.001). Using data from the STOP CRC study of 26 community clinics, our team developed a risk prediction model that can stratify patients according to their probability of adherence with follow-up colonoscopy. Our study will answer a key pragmatic question: can patient navigation effectively improve follow-up colonoscopy among patients who have a moderate or low probability of adhering to follow-up colonoscopy; and secondarily, does the effectiveness of patient navigation differ by patients? probability level? We will build on our successful ongoing research to test a patient-level intervention, driven by the Chronic Care Model, to increase diagnostic follow-up for colorectal cancer screening. In Aim 1, we will validate the risk prediction model, stratify patients according to risk, and adapt patient navigation materials to local resources and settings. In Aim 2, we will conduct a two-arm randomized-controlled trial involving 28 clinics (~1200 patients with positive fecal tests) and will compare patient navigation and usual care in raising rates of follow-up colonoscopy. We will assess the effectiveness (completion of colonoscopy within 1 year) of the program overall, as well as the effectiveness by category of probability of adherence to follow-up colonoscopy (moderate vs. low). This large-scale, clinic-randomized, two-arm follow-up colonoscopy program among safety net patients will leverage the expertise of our research team, which has implemented numerous systems-based interventions in multiple health care settings and used electronic health record tools to deliver clinic-based interventions. We will build on these successes in undertaking the largest study to-date addressing follow-up colonoscopy uptake among patients who receive care in safety net clinics. This study could optimize the delivery of patient navigation, support the broad adoption of patient navigation programs, and greatly improve colonoscopy follow-up rates in this vulnerable population.